Abstract
Background
Odontogenic lesions constitute a heterogeneous group of lesions. CLIC4 protein regulates different cellular processes, including epithelial-mesenchymal transition and fibroblast-myofibroblast transdifferentiation. This study analyzed CLIC4, E-cadherin, Vimentin, and α-SMA immunoexpression in epithelial odontogenic lesions that exhibit different biological behavior.
Methods
It analyzed the immunoexpression of CLIC4, E-cadherin, and Vimentin in the epithelial cells, as well as CLIC4 and α-SMA in the mesenchymal cells, of ameloblastoma (AM) (n = 16), odontogenic keratocyst (OKC) (n = 20), and adenomatoid odontogenic tumor (AOT) (n = 8). Immunoexpressions were categorized as score 0 (0% positive cells), 1 (< 25%), 2 (≥ 25% - < 50%), 3 (≥ 50% - < 75%), or 4 (≥ 75%).
Results
Cytoplasmic CLIC4 immunoexpression was higher in AM and AOT (p < 0.001) epithelial cells. Nuclear-cytoplasmic CLIC4 was higher in OKC’s epithelial lining (p < 0.001). Membrane (p = 0.012) and membrane-cytoplasmic (p < 0.001) E-cadherin immunoexpression were higher in OKC, while cytoplasmic E-cadherin expression was higher in AM and AOT (p < 0.001). Vimentin immunoexpression was higher in AM and AOT (p < 0.001). Stromal CLIC4 was higher in AM and OKC (p = 0.008). Similarly, α-SMA immunoexpression was higher in AM and OKC (p = 0.037). Correlations in these proteins’ immunoexpression were observed in AM and OKC (p < 0.05).
Conclusions
CLIC4 seems to regulate the epithelial-mesenchymal transition, modifying E-cadherin and Vimentin expression. In mesenchymal cells, CLIC4 may play a role in fibroblast-myofibroblast transdifferentiation. CLIC4 may be associated with epithelial odontogenic lesions with aggressive biological behavior.



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The authors declare that the data supporting this study’s findings are available from the corresponding author upon reasonable request.
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M.C.X., C.C.S.B., and M.R.S.M.: conceptualization, investigation, data curation, writing—original draft, review, and editing. R.P.M.: formal analysis, writing—review & editing. H.F.L.: investigation, writing—review & editing. É.J.D.S. and A.L.L.C.: conceptualization, supervision, writing—review & editing. All authors read and approved the manuscript.
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Xerez, M.C., da Silva Barros, C.C., de Souto Medeiros, M.R. et al. CLIC4 Function in the Epithelial-Mesenchymal Transition of Epithelial Odontogenic Lesions. Head and Neck Pathol 18, 40 (2024). https://doi.org/10.1007/s12105-024-01646-1
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DOI: https://doi.org/10.1007/s12105-024-01646-1